Hsu H C, Enosawa S, Yamazaki T, Tohyama S, Fujita J, Fukuda K, Kobayashi E
Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan; Division of Advanced Medical Sciences, National Center for Child Health and Development, Tokyo, Japan.
Division of Advanced Medical Sciences, National Center for Child Health and Development, Tokyo, Japan; Kohno Clinical Medicine Research Institute, Tokyo, Japan.
Transplant Proc. 2017 Jan-Feb;49(1):153-158. doi: 10.1016/j.transproceed.2016.11.023.
With the goal of in vivo cultivation of human hepatocytes that have not been sufficient in full differentiation in vitro, the advantage of neonatal thymectomy was verified on expansion of xenogeneic human hepatocyte in the micro-miniature pig (MMP).
The thymus was excised immediately after the birth of the MMPs via cesarean section. Newborns were fed by artificial feeding under specific pathogen-free conditions. The thymectomized and nonthymectomized littermates were transplanted with human hepatocytes via a portal vein with or without partial hepatectomy at the MMP adult stage.
The growth of thymectomized MMPs and the sham operated littermates was not significantly different; the former weighed 1.98 ± 0.30 kg (average ± standard deviation, n = 4) and the latter weighed 2.28 ± 0.39 kg (n = 4) at 1 month of age, and 17.48 ± 1.92 kg and 16.75 ± 2.68 kg at 12 months of age. Blood thymosin α concentrations in the thymectomy group were significantly lower than in the control group (0.22 ± 0.05 ng/mL vs 0.46 ± 0.16 ng/mL; n = 4, 12 months old, P = .029). After human hepatocyte transplantation, human albumin levels were detectable on day 28 in the peripheral blood of the thymectomy plus hepatectomy group (14.3 ± 4.9 ng/mL [± range, n = 2]) but were not detectable even on day 21 in the control group.
Neonatal thymectomy was successfully achieved in infantile MMPs born via cesarean section. These pigs were considered to be an ideal in vivo bioreactor for human hepatocytes.
为了实现体外分化不完全的人肝细胞的体内培养，在微型猪（MMP）中验证了新生期胸腺切除术对异种人肝细胞扩增的优势。
通过剖宫产在MMP出生后立即切除胸腺。在无特定病原体条件下对新生仔猪进行人工喂养。在MMP成年期，对胸腺切除和未切除胸腺的同窝仔猪通过门静脉进行人肝细胞移植，部分仔猪同时进行或不进行部分肝切除术。
胸腺切除的MMP与假手术同窝仔猪的生长情况无显著差异；1月龄时，前者体重为1.98±0.30千克（平均值±标准差，n = 4），后者体重为2.28±0.39千克（n = 4）；12月龄时，分别为17.48±1.92千克和16.75±2.68千克。胸腺切除组的血胸腺素α浓度显著低于对照组（0.22±0.05纳克/毫升对0.46±0.16纳克/毫升；n = 4，12月龄，P = 0.029）。人肝细胞移植后，胸腺切除加肝切除组外周血在第28天可检测到人白蛋白水平（14.3±4.9纳克/毫升[±范围，n = 2]），而对照组即使在第21天也未检测到。
通过剖宫产出生的幼年MMP成功实现了新生期胸腺切除术。这些猪被认为是用于人肝细胞的理想体内生物反应器。
